What are the diagnostic steps for testing sarcoidosis?

Diagnostic Testing for Sarcoidosis

The diagnosis of sarcoidosis requires a compatible clinical presentation, evidence of noncaseating granulomatous inflammation in one or more tissue samples, and exclusion of alternative causes of granulomatous disease. 1

Initial Diagnostic Steps

Clinical Assessment

• Evaluate for highly probable clinical features:
  • Löfgren's syndrome (bilateral hilar adenopathy with erythema nodosum and/or periarticular arthritis)
  • Lupus pernio (violaceous skin lesions)
  • Uveitis
  • Optic neuritis
  • Erythema nodosum 1

Imaging Studies

1. Chest Imaging:

   • High-resolution computed tomography (HRCT) is preferred over chest X-ray due to higher resolution 2
   • Look for characteristic findings:
     • Bilateral hilar adenopathy
     • Perilymphatic nodules
     • Upper lobe or diffuse infiltrates
     • Peribronchial thickening 1

2. Additional Imaging (based on suspected organ involvement):

   • Cardiac MRI (preferred) or PET-CT for suspected cardiac involvement 3
   • MRI with gadolinium enhancement for suspected CNS involvement 1
   • CT/MRI/PET for suspected liver, spleen, or bone involvement 1

Laboratory Testing

1. Required Baseline Tests:

   • Serum calcium (strong recommendation) 1
   • Serum creatinine 1
   • Serum alkaline phosphatase 1
   • ECG (for all patients, even without cardiac symptoms) 1

2. Additional Tests (based on clinical suspicion):

   • 25-OH and 1,25-OH vitamin D levels (if vitamin D assessment needed) 1
   • BAL (bronchoalveolar lavage) fluid analysis to exclude infections/malignancy and assess CD4:CD8 ratio 1
   • ACE (angiotensin-converting enzyme) level (elevated in many cases but not diagnostic) 1

Tissue Sampling

When to Obtain Tissue:

• Tissue sampling is NOT recommended when there is high clinical suspicion for sarcoidosis with classic presentations (e.g., Löfgren's syndrome, lupus pernio) 1
• For all other cases, tissue confirmation is necessary

Sampling Methods:

• Lymph Node Sampling:

  • Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for mediastinal/hilar lymphadenopathy
  • Superficial lymph node biopsy when accessible

• Lung Tissue Sampling:

  • Transbronchial lung biopsy
  • Transbronchial cryobiopsy
  • Surgical lung biopsy (when less invasive methods are non-diagnostic)

• Other Organ Sampling:

  • Skin biopsy for cutaneous lesions
  • Endomyocardial biopsy for cardiac involvement (limited sensitivity 25-50%) 3

Organ-Specific Diagnostic Evaluation

Cardiac Sarcoidosis

• Baseline ECG for all patients 1, 3
• For suspected cardiac involvement:
  • Cardiac MRI with late gadolinium enhancement (first-line) 3
  • PET-CT with fluorodeoxyglucose (if MRI unavailable) 3
  • Echocardiography to assess ventricular function 3
  • 24-hour Holter monitoring to detect arrhythmias 3

Pulmonary Hypertension

• Initial testing with transthoracic echocardiography when PH is suspected 1

Exclusion of Alternative Diagnoses

• Infectious Causes: Mycobacterial and fungal cultures/stains
• Malignancy: Appropriate imaging and cytological evaluation
• Beryllium Disease: Blood lymphocyte proliferation test 1
• Vasculitis: MPO and PR3 antineutrophil cytoplasmic antibodies
• IgG4-Related Disease: Serum IgG4 levels and IgG4:IgG ratio 1

Diagnostic Algorithm

1. Assess clinical presentation for highly probable features of sarcoidosis
2. Perform initial imaging (HRCT of chest)
3. Conduct baseline laboratory tests (calcium, creatinine, alkaline phosphatase, ECG)
4. Determine need for tissue sampling:
   • If classic presentation (Löfgren's syndrome, lupus pernio) → no biopsy needed
   • Otherwise → obtain appropriate tissue samples
5. Exclude alternative diagnoses through appropriate testing
6. Evaluate for specific organ involvement based on symptoms and initial findings
7. Monitor disease activity with appropriate follow-up testing

Pitfalls and Caveats

• Diagnosis of sarcoidosis is never fully secure and requires ongoing assessment 1
• Negative endomyocardial biopsy does not exclude cardiac sarcoidosis due to sampling error 3
• BAL fluid analysis alone is insufficient for diagnosis but can help exclude other conditions 1
• Sarcoidosis can mimic other conditions on imaging, including interstitial lung diseases, tuberculosis, and malignancy 2
• A thorough clinical and radiological evaluation, definite biopsy showing non-caseating granulomas, and exclusion of similar conditions are all necessary before confirming diagnosis 2